Because of their ability to bind an antigen with a high degree of specificity, monoclonal antibodies are widely used as research, diagnostic, and therapeutic reagents. In addition to their specific binding to an antigen, monoclonal antibodies may activate the complement system and effector cells through their Fc region. In order to properly interpret an antibody's biological properties, proper controls are essential. Without proper controls, it is difficult to establish a causal relationship between an antibody's specific binding activity and the biochemical and biological effects of the antibody.
Control monoclonal antibodies currently in use include: 1. antibodies secreted by naturally occurring plasmacytoma, with no known target antigens; 2. antibodies raised against antigens from evolutionarily distant species, such as KLH (keyhole limpet hemocyanin); 3. antibodies reactive with a known target antigen that is distinct from the antigen of interest.
In each of these cases, the control antibodies used have a poorly defined variable domain and uncertain antigen specificities. And in the third case, there remains the issue of cross reactivity. Because of this, it is not uncommon to encounter problems such as cross reactivity or non-specific binding when currently available control antibodies are used. Furthermore, due to the lack of an ideal control antibody, research is often performed using formulation vehicles, such as normal saline, as a control. In such cases, it is difficult, if not impossible, to distinguish whether an observed biochemical and/or biological effect is a direct result of the specific antigen/antibody interaction, or a result of nonspecific effects, such as interactions and biological effects of other parts of the antibody molecule or contaminants present in the antibody preparation, such as the host cell proteins. For at least these reasons, there is currently a great need for improved, rationally designed control antibodies.